A shape analysis framework for neuromorphometry

This paper addresses in an integrated and systematic fashion the relatively overlooked but increasingly important issue of measuring and characterizing the geometrical properties of nerve cells and structures, an area often called neuromorphology. After discussing the main motivation for such an endeavour, a comprehensive mathematical framework for characterizing neural shapes, capable of expressing variations over time, is presented and used to underline the main issues in neuromorphology. Three particularly powerful and versatile families of neuromorphological approaches, including differential measures, symmetry axes/skeletons, and complexity, are presented and their respective potentials for applications in neuroscience are identified. Examples of applications of such measures are provided based on experimental investigations related to automated dendrogram extraction, mental retardation characterization, and axon growth analysis.     

A Golgi localization signal identified in the Menkes recombinant protein

Menkes disease arises from a genetic impairment in copper transport. The gene responsible for the phenotype has been identified as a copper transporting ATPase ( ATP7A ). Recently, the protein encoded by the ATP7A gene has been localized to the Golgi complex. In order to investigate the role of the Menkes disease protein in copper transport, recombinant constructs containing both the full-length open reading frame and an alternatively spliced form have been successfully expressed and localized in mammalian cells. Other studies of a patient with occipital horn syndrome, an allelic variant of Menkes disease, have demonstrated that only this alternatively spliced isoform and not the full-length form is expressed in this patient. The milder form of this patient's phenotype suggests that the alternatively spliced isoform has some functional role in copper transport. In the present study the full-length recombinant Menkes protein was shown by immunofluorescence to localize to the Golgi apparatus and the alternatively spliced form, lacking sequences for transmembrane domains 3 and 4 encoded by exon 10, was shown to localize to the endoplasmic reticulum. Using sequences from exon 10 fused to a non-Golgi reporter molecule, a 38 amino acid sequence containing transmembrane domain 3 of the Menkes protein was found to be sufficient for localization to the Golgi complex. Therefore, the protein sequence encoded by exon 10 may be responsible for this differential localization and both isoforms may be required for comprehensive transport of copper within the cell.     

Evolution of PZC with thermal transformation of Tunisian kaolinite

The purpose of this paper is to study the thermal behaviour of Na⁺-saturated Tunisian kaolinite (ka-Tab) with the evolution of its point of zero charge (PZC). The Fourier Transform Infrared spectroscopy (FTIR), X-Ray Diffraction (XRD), Differential Thermal Analysis (DTA), Cation Exchange Capacity (CEC) and specific surface area (SSA) were used to characterize the kaolinite sample. In the present investigation, the focus was on the surface charge characteristics of kaolinite at different temperature of heating. The results show that the formation of new phases in the kaolinite structure at temperature >500–600°C, shifts the PZC value towards 8 which approximately PZC value of α-Al₂O₃. The article is published in the original.     

Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas

Hepatocellular carcinoma (HCC) is the major primary malignant tumor in the human liver, but the molecular changes leading to liver cell transformation remain largely unknown. The Wnt-beta-catenin pathway is activated in colon cancers and some melanoma cell lines, but has not yet been investigated in HCC. We have examined the status of the beta-catenin gene in different transgenic mouse lines of HCC obtained with the oncogenes c-myc or H-ras. Fifty percent of the hepatic tumors in these transgenic mice had activating somatic mutations within the beta-catenin gene similar to those found in colon cancers and melanomas. These alterations in the beta-catenin gene (point mutations or deletions) lead to a disregulation of the signaling function of beta-catenin and thus to carcinogenesis. We then analyzed human HCCs and found similar mutations in eight of 31 (26%) human liver tumors tested and in HepG2 and HuH6 hepatoma cells. The mutations led to the accumulation of beta-catenin in the nucleus. Thus alterations in the beta-catenin gene frequently are selected for during liver tumorigenesis and suggest that disregulation of the Wnt-beta-catenin pathway is a major event in the development of HCC in humans and mice.     

An ultrasonic method for measuring tissue displacement: technicaldetails and validation for measuring myocardial thickening

We have developed a method for measuring myocardial thickening from a single ultrasonic transducer attached to the epicardium. Displacement of the underlying myocardial tissue is measured by following the phase of the echoes within a sample volume range-gated across the myocardium. The output is in the form of an analog signal. To verify the accuracy, resolution, and limitations of the system, we derived the equations relating the position of a reflector to the phase of its echo and compared the system output in vitro to a known input using a single moving target and a random distribution of scatterers, and in vivo to that of an ultrasonic transit-time dimension gauge. The results demonstrate that the 10 MHz system can accurately follow the motion of single or multiple targets with a resolution of 0.02 mm. In 25 dogs myocardial thickening measured with the displacement system compared favorably in both waveform and magnitude with thickening measured by the two-crystal transit-time method. Applications for the displacement method include: quantification of regional ventricular function in animal models of cardiovascular diseases, measurement of endocardial to epicardial differences in the deformation of regional myocardium during the cardiac cycle, and evaluation of regional cardiac function in patients during and after corrective cardiac surgery.     

Pyramid-shaped silicon photodetector with subwavelength aperture[for NSOM]

We present a new type of silicon photodetector with a subwavelength aperture designed to scan material surfaces with a resolution inaccessible by conventional optical microscopy. Such a probe is designed for integration into a near-field scanning optical microscope (NSOM) for scanning and collecting information from the near-field region located at the vicinity of the surface. The photodetector, which was realized by conventional microelectronics technology, is located on top of a 250-μm-high pyramid, enabling detection of reflected as well as transmitted light. The light sensitive part of the probe consists of a micromachined silicon structure built using anisotropic etch solutions such as ethylene diamine pyrocatechol (EDP) and KOH. The shape of the probe is a truncated double pyramid with a ring shape top silicon/aluminum Schottky diode surrounding an exposed silicon photosensitive area of about 150 nm in diameter. Typical I-V characteristics and optical response measurements are presented     

Identification by STS PCR screening of a microdeletion in Xp21.3-22.1 associated with non-specific mental retardation

X-linked non-specific mental retardation (MRX) is a heterogeneous condition in which mental retardation (MR) appears to be the only consistent manifestation. The genetic and phenotypic heterogeneity exclude any possibility of pooling families and, therefore, of fine-mapping the related disease genes. In order to identify genomic critical regions involved in the MRX condition assigned to Xp21.3-22.1 region, we have implemented the PCR screening of non fragile X MR patients for the presence of deletions in this region. The amplification by PCR of 12 markers located between POLA and DXS704 using genomic DNA from 192 MR males led to the identification, in a 9 year old mentally retarded boy, of a microdeletion which extends from DXS1202 to DXS1065. None of the known genes, POLA, MAGE genes cluster, DAX1, GK and DMD, that map in the Xp21.3-22.1 region is affected by this deletion. This approach, which could easily be applied to several other MRX loci, allowed not only a confirmation of the presence of a potential locus in Xp21.3-22.1 involved in non-specific mental retardation, but also a better definition of the genomic critical region corresponding to this locus.